Chemical structure of thyroxine
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Liothyronine Sodium

The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are tyrosine-based hormones produced by the thyroid gland. An important component in the synthesis is iodine. The major form of thyroid hormone in the blood is thyroxine (T4). This is converted to the active T3 within cells by deiodinases. These are further processed by decarboxylation and deiodination to produce iodothyronamine (T1a) and thyronamine (T0a). more...

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Circulation

Most of the thyroid hormone circulating in the blood is bound to transport proteins :

  • Thyroxine-binding globulin (TBG)
  • Thyroid-binding prealbumin (TBPA) - this protein is also responsible for the transport of retinol, and so now has the preferred name of transthyretin (TTR)
  • albumin.

Only a very small fraction of the circulating hormone is free (unbound) - T4 0.03% and T3 0.3%. This free fraction is biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value. These values are referred to as fT4 and fT3. Another critical diagnostic tool is the amount of thyroid-stimulating hormone that is present. When thyroid hormone is bound, it is not active, so the amount of free T3/T4 is what is important. For this reason, measuring total thyroxine in the blood can be misleading.

Function

The thyronines act on the body to increase the basal metabolic rate, affect protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline).The thyroid hormones are essential to proper development and differentiation of all cells of the human body. To various extents, they regulate protein, fat and carbohydrate metabolism. But they have their most pronounced effects on how human cells use energetic compounds. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.

The thyronamines function via some unknown mechanism to inhbit neuronal activity; this plays an important role in the hibernation cycles of mammals. One effect of administering the thyronamines is a severe drop in body temperature.

Related diseases

Both excess and deficiency of thyroxine can cause disorders.

  • Thyrotoxicosis or hyperthyroidism is the clinical syndrome caused by an excess of circulating free thyroxine, free triiodothyronine, or both. It is a common disorder that affects approximately 2% of women and 0.2% of men.
  • Hypothyroidism is the case where there is a deficiency of thyroxine.

Medical use of thyroid hormones

Both T3 and T4 are used to treat thyroid hormone deficiency (hypothyroidism). They are both absorbed well by the gut, so can be given orally. Levothyroxine, the most commonly used form, is a stereoisomer of physiological thyroxine, which is metabolised more slowly and hence usually only needs once-daily administration.

Thyronamines have no medical usages yet, though their use has been proposed for controlled induction of hypothermia which causes the brain to enter a protective cycle, useful in preventing damage during ischemic shock.

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Laboratory diagnosis of factitious disorders - adapted from the Archives of Internal Medicine, August 8, 1994 - Tips from Other Journals
From American Family Physician, 11/1/94

A factitious disorder is the intentional feigning or production of physical symptoms. It is estimated that 5 percent of physician-patient encounters may involve this diagnosis. Factitious disorder, commonly referred to as Munchausen syndrome, may not be suspected until after contradictory laboratory findings are found during the work-up for the feigned illness. Wallach reviewed the literature published since 1965 to identify the major features of factitious disorders.

Factitious disorders must be distinguished from other conditions such as malingering, conversion disorder, hypochondriasis and artifactual laboratory results. The hallmark of the disorder is factitious illness. In children, factitious illness may be produced by another person, almost always the mother. In this context, it can be classified as child abuse.

The fabricated history may appear plausible, but specific details are usually vague or inconsistent. Heroic deeds may be included in the history. Patients will often have extremely thick charts and clinical evidence of multiple surgeries. The usual time of onset is early adult life. The patients are typically demanding, hostile and attention-seeking. A remarkable aspect of the disorder is the willingness of patients to undergo endless laboratory testing and painful surgical procedures.

Recurrent themes appear in this disorder. A failure to suspect and diagnose the disorder is common. Factitious disorder is usually diagnosed during the process of evaluating the suspected illness that is being feigned. Scarce resources are wasted when unnecessary tests are ordered in pursuit of a diagnosis. Up to 12,000 patients with this disorder are hospitalized annually, at a cost of up to $40 million.

Patients have a general resistance to psychiatric therapy and, even if therapy is sought, the results are usually unsatisfactory with a high rate of recurrence. Clinicians easily become overwhelmed and angered by these frustrating patients. Factitious disorder has resulted in patient death, simulated rape and murder, although these instances are rare. The scope of the disorder crosses all areas of health care delivery and involves primary care physicians, sub-specialists and ancillary personnel.

Laboratory tests are often the only way to diagnose a factitious disorder, and discordant results should heighten the suspicion of the diagnosis. Clinicians should be aware of and use the sophisticated laboratory tests that are currently available. These tests can accurately assay minute amounts of chemicals and foreign substances in the blood and aid in diagnosis of the disorder. The accompanying table lists examples of factitious disorder in which the laboratory plays a role.

The author concludes that laboratory studies may provide essential objective information for the clinician when factitious disorder is suspected. Early recognition can prevent unnecessary testing and procedures. The primary physician who is aware of new, sophisticated laboratory assays may be able to confirm an early initial diagnosis rather than making a diagnosis by exclusion and wasting valuable resources.

COPYRIGHT 1994 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group

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